Is ANK3 p.Ala1737Val (c.5210C>T) pathogenic?

ANK3 p.Ala1737Val (c.5210C>T) is classified Uncertain significance in ANK3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-11). AlphaMissense: likely benign (0.1161); Ultra-rare (popmax 0.0165%, mid).

How common is ANK3 p.Ala1737Val (c.5210C>T) in the general population?

ANK3 p.Ala1737Val (c.5210C>T) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

What do computational predictors say about ANK3 p.Ala1737Val (c.5210C>T)?

AlphaMissense predicts likely benign (score 0.1161) — an in-silico prediction, not a clinical call.

ANK3 p.Ala1737Val

c.5210C>T · rs766671422 · VCV1431568

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1161 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Computational evidence

Protein change
AlphaMissense	0.1161	likely benign
REVEL	0.177	moderately benign-leaning
⇒ AlphaMissense and REVEL both call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.7	GERP 5.5, phastCons 1
Regional constraint	o/e 0.86	unconstrained · MANE · 7,641 bp · p 6.9e-05 · regional, not allelic
Overall
CADD	24.2	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0165% Middle Eastern · 1/6,060 alleles

Filtering AF 0.00437% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0038%

Overall 0.00452% 73/1,614,116 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,060
South Asian	0.00878%	11,386
European (non-Finnish)	0.00525%	19,032
Admixed American	0.00167%	60,020
Remaining individualsnot grpmax-eligible	0.0016%	62,506

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: ANK3
Protein: p.Ala1737Val
Coding: c.5210C>T
MANE Select: NM_020987
dbSNP: rs766671422
Type: single nucleotide variant
Location: chr10:60075671 (GRCh38)
Gene constraint: LOEUF 0.16 · pLI 1.00 (gnomAD)

Full ANK3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ANK3 c.2382+6C>T Uncertain significance ★★ same type
ANK3 p.Ala1461Thr Uncertain significance ★★ ⚠ same type
ANK3 p.Ala1534Val Uncertain significance ★★ same type
ANK3 p.Ala1630Val Uncertain significance ★★ ⚠ same type
ANK3 p.Ala169Thr Uncertain significance ★★ same type
ANK3 p.Ala2023Thr Uncertain significance ★★ ⚠ same type
ANK3 p.Ala218Thr Uncertain significance ★★ same type
ANK3 p.Ala2223Thr Uncertain significance ★★ ⚠ same type

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/ank3-p-ala1737val (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown